Probing the polarity of spontaneous GABAergic synaptic transmission in vivo

Neuronal chloride gradient directly affects the polarity of GABAergic transmission, a major factor of network dysfunction in a variety of brain pathologies. But the influence of [Cl-]i on functional GABAergic transmission critically depends on the very dynamic combination of membrane potential, conductance and occurrence of other synaptic inputs. Taking this complexity into account implies measuring the postsynaptic responses to spontaneously occurring GABAergic events, in vivo, without interfering with neuronal [Cl-]i. We have overcome this challenge by combining extracellular detection of unitary inhibitory postsynaptic field-potentials (fIPSPs) and silicon probe recording of the firing activity of multiple individually identified neurons. Probing the polarity of spontaneous, ongoing GABAergic transmission across the CA3 hippocampal circuit in vivo with single cell resolution, our results support depolarizing actions of perisomatic GABAergic transmission and time-locked excitation of CA3 pyramidal neurons in acute and chronic mouse models of epilepsy, but little contribution of excitatory GABA to epileptogenesis.